Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response.

Funk CJ, Manzer R, Miura TA, Groshong SD, Ito Y, Travanty EA, Leete J, Holmes KV, Mason RJ.

Citation

Funk CJ, Manzer R, Miura TA, Groshong SD, Ito Y, Travanty EA, Leete J, Holmes KV, Mason RJ. (2009) Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response. Journal of General Virology 90(Pt 12):2956-2964.

Abstract

The rat coronavirus sialodacryoadenitis virus (SDAV) causes respiratory infection and provides a system for investigating respiratory coronaviruses in a natural host. A viral suspension in the form of a microspray aerosol was delivered by intratracheal instillation into the distal lung of 6-8-week-old Fischer 344 rats. SDAV inoculation produced a 7 % body weight loss over a 5 day period that was followed by recovery over the next 7 days. SDAV caused focal lesions in the lung, which were most severe on day 4 post-inoculation (p.i.). Immunofluorescent staining showed that four cell types supported SDAV virus replication in the lower respiratory tract, namely Clara cells, ciliated cells in the bronchial airway and alveolar type I and type II cells in the lung parenchyma. In bronchial alveolar lavage fluid (BALF) a neutrophil influx increased the population of neutrophils to 45 % compared with 6 % of the cells in control samples on day 2 after mock inoculation. Virus infection induced an increase in surfactant protein SP-D levels in BALF of infected rats on days 4 and 8 p.i. that subsided by day 12. The concentrations of chemokines MCP-1, LIX and CINC-1 in BALF increased on day 4 p.i., but returned to control levels by day 8. Intratracheal instillation of rats with SDAV coronavirus caused an acute, self-limited infection that is a useful model for studying the early events of the innate immune response to respiratory coronavirus infections in lungs of the natural virus host.